NOTICE: Applications submitted in response to this
Funding Opportunity Announcement (FOA) for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424
(R&R) Application Guide.

APPLICATIONS MAY NOT
BE SUBMITTED IN PAPER FORMAT.

This FOA must be read
in conjunction with the application guidelines included with this announcement
in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process
is necessary before submission, and applicants are highly encouraged to start
the process at least four (4) weeks prior to the grant submission date. See Section IV.

Purpose.This FOA issued by the NHLBI, National Institutes of Health, solicits
Research Project Grant (R01) applications from institutions/ organizations
that propose to perform research that will enhance the understanding of
how the pre- and postnatal environments affect the interplay of the lung and immune system during development
resulting in sustained changes in lung physiology and immune function that
compromise respiratory health and outcomes.

Mechanism of Support. This FOA will utilize
the NIH Research
Project Grant (R01)award mechanism.

Funds Available and Anticipated Number of Awards.The NHLBI intends to commit
approximately $3.5 million in total costs in FY 2009,and up to $17.5 million over five years, to fund 6-8 grants
under this FOA. Awards issued
under this FOA are contingent upon the availability
of funds and the submission of a sufficient number of meritorious applications.

Budget and Project Period. Budgets for direct costs of up to
$350,000 per year (exclusive of indirect costs associated with consortia)
and a project duration of up to five years may
be requested for a maximum of $1,750,000 direct costs over a five-year
project period. Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the size and duration of each award will also vary. The
total amount awarded and the number of awards will depend upon the
numbers, quality, duration, and costs of the applications received.

Eligible Project Directors/Principal
Investigators (PDs/PIs). Individuals with the skills, knowledge, and
resources necessary to carry out the proposed research are invited to work
with their institution/organization to develop an application for support.
Individuals from underrepresented racial and ethnic groups as well as
individuals with disabilities are always encouraged to apply for NIH
support.

Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be
designated on the application.

Number of Applications. Applicants may submit more than one application,
provided each application is scientifically distinct.

Resubmissions. Resubmission applications are not permitted in response to
this FOA.

Renewals.Renewal
applications are not permitted in response to this FOA.

Lung diseases
are the fourth leading cause of death and disability in the United States and are associated
with a national economic burden of over 100 billion dollars per year. The
prevalence of many lung diseases continues to increase as current therapeutics focus primarily on symptom control rather than preventing
the initiation or progression of disease. One critical gap in knowledge that
contributes to the challenge of creating new therapeutic modalities that
address the disease defects is an incomplete understanding
of normal pulmonary and immune system development and the interplay between
these two systems. The fetus and infant undergo rapid growth and development
with pronounced changes in the pulmonary and immune systems that continue into
childhood. Due to the delicate regulation of these
developmental processes and, as a result of genetic and environmental factors,
many respiratory illnesses have their beginnings early in life. The exact
stimuli and mechanisms by which these early events affect disease susceptibility and, in some cases, promote lung
disease later in life are unknown. A thorough understanding is needed of the
interplay of the lung and immune system during development as well as how
environmental and genetic factors affect these developmental
processes.

Lung and immune
system development are extremely plastic and continue into the first years of
life. Developmental plasticity is affected by the pre- and postnatal
environments; thus, perinatal environmental stresses or insults interfere in normal developmental processes resulting in
permanently altered structure and/or function. Studies have shown that
sub-optimal pre- and postnatal environments exert specific long-term effects on
lung structure and function which persist and adversely
affect lung function, aging and respiratory health into adulthood. Such
exposures include: hyperoxia, hypoxemia, malnutrition, pre-term birth,
microbial colonization, infection and tobacco smoke. Similarly, the developing
immune system is modified by specific antigenic
exposures, diet, and infection both pre- and postnatally. Lung development is
influenced by the interaction between the immune system and resident lung
cells, nerves, and bronchial smooth muscle. Coordinated and balanced immune
and pulmonary development and function are critical
for the respiratory system, because the lung is continually exposed to changing
environmental factors and stresses. The study of the early origins of lung
disease is at a critical juncture where the lung and the
immune system must be studied simultaneously to understand how specific
physiologic stresses and environmental exposures alter lung and immune system
function with persistent effects on respiratory health and disease. The
ultimate goal is to identify early disease risk
markers and clinical outcomes based on disease mechanism rather than symptoms
and enable the rational development of early interventions to prevent or cure
lung disease.

The purpose of this R01 program is to promote multidisciplinary research to increase understanding of how pre- and postnatal environments affect the developing lung and immune system simultaneously resulting in sustained changes in lung physiology and immune function and sub-optimal respiratory health and outcomes. This program requires partnering of PIs with expertise in pulmonary development and immunology, appropriate to the developmental window proposed for study, to utilize an integrative and comprehensive approach to define molecular and cellular processes which result in sustained altered pulmonary physiology and immune system function. Other expertise may be added as necessary for a specific proposed project. Studies addressing pre- and/or postnatal development of the pulmonary and immune systems are appropriate. Applicants may propose to study any appropriate developmental stage from pre-natal through the prepubertal period. Animal models are appropriate in certain circumstances (e.g., for studies during the prenatal period or mechanistic studies that are inappropriate for children), but the applicant should state how studies will inform knowledge of pulmonary and immune system development in humans. A human studies research component is also required. These studies must have some mechanistic basis and not be solely descriptive. Mechanistically-based, longitudinal studies may be proposed for this program given the extended time frame of pulmonary and immune system development. Examples of studies that will NOT be considered responsive to this FOA are: long-term epidemiological studies without accompanying mechanistic studies and adult studies with retrospective analyses of risk factors and/or biomarkers. Applicants are encouraged to contact program staff to discuss responsiveness issues. If possible, a program should link study results with known phenotypes or biomarkers of lung disease or with disease mechanism.

Examples of research
objectives that are encouraged through this program include, but are not
limited to, the following:

Use of targeted
molecular techniques and genetic manipulations
to understand how alterations in the environment may cause reprogramming
of immune and pulmonary development (e.g., alveolar septation, function of
lung epithelium, maturation of immune phenotype, development of T regulatory cells) that lead to disease state.

Identification
of genetic and/or epigenetic alterations which affect the pulmonary and
immune developmental program to cause sustained changes in lung
physiology, increasing susceptibility to disease, in response to environmental stresses.

Elucidation of
how inflammatory stimuli affect development of acquired and innate immune
and pulmonary defense responses (e.g., chronic dysregulation of homing
pathways and effector inflammatory cells, effects on surfactants and defensins).

Genetic,
molecular, chemical, dietary or environmental manipulation used to
determine if normal immune and/or pulmonary development can be restored
when perturbed by environmental stress.

Discovery of
the innate immune or acquired responses to maternal,
fetal, or postnatal exposures that play an important role in host
susceptibility, disease pathogenesis, and diversity of clinical expression
in the developing lung

Determination
of the pathways involved in inappropriate immune and structural responses in the lung during development which lead to
disease or increased susceptibility.

Identification
of the windows of increased vulnerability of the developmental interplay
of lung and immune systems to specific environmental exposures.

This FOA will
use theR01 award mechanism. The Project
Director/Principal Investigators (PD/PI) will be solely responsible for
planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts (see SF424 (R&R)
Application Guide). It also uses the modular as well as the
non-modular budget formats (seehttp://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, a U.S. organization submitting an application with direct costs
in each year of $250,000 or less (excluding consortium Facilities and
Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than
$250,000 in annual direct costs and all Foreign applicants must complete and
submit budget requests using the Research & Related Budget component.

2.
Funds Available

The
NHLBI intends to award up to $17.5 million over five years under this FOA.
Awards issued under this FOA are contingent upon the
availability of funds and the submission of a sufficient number of meritorious
applications.

It is
anticipated that 6-8 awards will be made under this FOA.

Budgets for
direct costs of up to $350,000 per year (exclusive of indirect costs
associated with consortia) and a project
duration of up to five years may be requested for a maximum of $1,750,000
direct costs over a five-year project period.

Because the
nature and scope of the proposed research will vary from application to
application, it is anticipated that the size and duration of each award will
also vary. Although the financial plans of the IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the
availability of funds.

Facilities
and Administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation. See NOT-OD-05-004.

The
decision of whether to apply for a grant with a single PD/PI or multiple
PDs/PIs grant is the responsibility of the investigators and applicant
organizations and should be determined by the scientific goals of the project.
Applications for grants with multiple PDs/PIs will require additional
information, as outlined in the instructions below. The NIH review criteria for
approach, investigators, and environment have been modified to accommodate
applications involving either a single PD/PI or multiple PDs/PIs. When
considering the multiple PD/PI option, please be aware that the structure and
governance of the PD/PI leadership team as well as the knowledge, skills and
experience of the individual PDs/PIs will be factored into the assessment of
the overall scientific merit of the application. Multiple PDs/PIs on a project
share the authority and responsibility for leading and directing the project,
intellectually and logistically. Each PD/PI is responsible and accountable to
the grantee organization, or, as appropriate, to a collaborating organization,
for the proper conduct of the project or program, including the submission of
required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

Each application is
encouraged to use the multiple principal investigators option
(http://grants.nih.gov/grants/multi_pi/index.htm); each application is expected
to be comprised of a partnership between a lead principal
investigator with expertise in pulmonary development and a lead principal
investigator with expertise in immunology. The investigators may be from
either the same or different institutions. The two PIs will share the
authority and responsibility for the scientific and
technical direction of the research project.

In order to be
considered responsive to this FOA applicants must include:

Multiple PIs—one PI
must have expertise in pulmonary development. The other PI must have
expertise in immunology appropriate to the developmental window proposed
for study.

A project that asks
research questions regarding how environmental exposures affect the
interplay of the immune system and pulmonary development and how these
alterations affect development of disease. Applications that consider
either the immune system or pulmonary development independently, with no
attempt to address the interplay between them, will be considered
unresponsive.

A mechanistically
based human subjects research component.

A project that
utilizes animals and human subjects/cells/tissues appropriate to the
developmental window defined in the application. This may be any time
during the prenatal, postnatal or prepubertal time periods in animals or
humans.

Applicants are not permitted to submit a
resubmission application in response to this FOA.

Renewal
applications are not permitted in response to this FOA.

Applicants
may submit more than one application, provided each application is
scientifically distinct.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for
Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned
the PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must
hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an NIH Internet Assisted Review (IAR) role, both roles should
exist under one Commons account.

All PDs/PIs at the applicant
organization must be affiliated with that organization. PDs/PIs located at
another institution need not be affiliated with the applicant organization, but
must be affiliated with their own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PDs/PI(s) and
AOR/SO need separate accounts in the NIH eRA Commons since both are authorized
to view the application image.

Note that if a PD/PI is
also an NIH peer reviewer with an Individual DUNS and CCR registration, that
particular DUNS number and CCR registration are for the individual reviewer
only. These are different than any DUNS number and CCR registration used by an
applicant organization. Individual DUNS and CCR registration should be used
only for the purposes of personal reimbursement and should not be used on any
grant applications submitted to the Federal Government.

Several of the steps of
the registration process could take four weeks or more. Therefore, applicants
should immediately check with their business official to determine whether
their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.

Prepare all
applications using the SF424 (R&R) application forms and in accordance with
the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

The SF424 (R&R)
Application Guide is critical to submitting a complete and accurate application
to NIH. Some fields within the SF424 (R&R) application components, although
not marked as mandatory, are required by NIH (e.g., the “Credential” log-in
field of the “Research & Related Senior/Key Person Profile” component must
contain the PD/PI’s assigned eRA Commons User ID). Agency-specific
instructions for such fields are clearly identified in the Application Guide.
For additional information, see “Frequently Asked Questions – Application
Guide, Electronic
Submission of Grant Applications.”

The SF424 (R&R)
application has several components. Some components are required, others are
optional. The forms package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Proposed research should provide special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions in other countries that are not
readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL
INSTRUCTIONS

Applications with
Multiple PDs/PIs

When
multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the
"Contact” PI, who will be responsible for all communication between the
PDs/PIs and the NIH, for assembling the application materials outlined below,
and for coordinating progress reports for the project. The contact PD/PI must
meet all eligibility requirements for PD/PI status in the same way as other
PDs/PIs, but has no other special roles or responsibilities within the project
team beyond those mentioned above.

Information
for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
“PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the
“Credential” field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application
to be rejected.

All projects
proposing Multiple PDs/PIs will be required to include a new section describing
the leadership plan approach for
the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled “Multiple PD/PI Leadership Plan”
[Section 14 of the Research Plan Component in the SF424 (R&R)], must be
included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators. If budget allocation is planned, the
distribution of resources to specific components of the project or the
individual PDs/PIs should be delineated in the Leadership Plan. In the event
of an award, the requested allocations may be reflected in a footnote on the
Notice of Award (NoA).

Applications Involving a
Single Institution

When all PDs/PIs are
within a single institution, follow the instructions contained in the SF424
(R&R) Application Guide.

Applications Involving
Multiple Institutions

When
multiple institutions are involved, one institution must be designated as the
prime institution, and funding for the other institution(s) must be requested
via a subcontract to be administered by the prime institution. When submitting
a detailed budget, the prime institution should submit its budget using the
Research & Related Budget component. All other institutions should
have their individual budgets attached separately to the Research & Related
Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward
budget form.

When
submitting a modular budget, the prime institution completes the PHS398 Modular
Budget component only. Information concerning the consortium/subcontract
budget is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 5.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research

Name, address, and telephone number of the
PD(s)/PI(s)

Names of other key personnel

Participating institutions

Number and title of this funding opportunity

Although
a letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows IC
staff to estimate the potential review workload and plan the review.

In order to expedite the
review, applicants are requested to notify the NHLBIReferral Office by email (nhlbichiefreviewbranch@nhlbi.nih.gov)when the application has been submitted. Please include the
FOA number and title, PD/PI name, and title of the application.

3.C.
Application Processing

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s)
and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully
submitted through Grants.gov, any errors have been addressed, and the assembled
application has been created in the eRA Commons, the PD/PI and the Authorized Organization
Representative/Signing Official (AOR/SO) have two weekdays (Monday–Friday,
excluding Federal holidays) to view the application image to determine if any
further action is necessary.

If everything is acceptable, no
further action is necessary. The application will automatically
move forward to the Division of Receipt and Referral in the Center for
Scientific Review for processing after two weekdays, excluding Federal holidays.

Prior to the submission deadline, the
AOR/SO can “Reject” the assembled application and submit a
changed/corrected application within the two-day viewing window. This
option should be used if it is determined that some part of the
application was lost or did not transfer correctly during the submission
process, the AOR/SO will have the option to “Reject” the application and
submit a Changed/Corrected application. In
these cases, please contact the eRA Help Desk to ensure that the issues
are addressed and corrected. Once rejected, applicants should follow the
instructions for correcting errors in Section 2.12, including the
requirement for cover letters on late applications. The
“Reject” feature should also be used if you determine that warnings are
applicable to your application and need to be addressed now. Remember,
warnings do not stop further application processing. If an application
submission results in warnings (but no errors), it will automatically move
forward after two weekdays if no action is taken. Some warnings may
need to be addressed later in the process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course
of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two weekdays.

Upon receipt, applications will be evaluated for
completeness by the CSR and responsiveness by the IC. Incomplete and
non-responsive applications will not be reviewed.

There
will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO
receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific
Review Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
the application status in the Commons.

The
NIH will not accept any application in response to this funding opportunity
that is essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an “Introduction” describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its
own risk and without NIH prior approval, incur obligations and expenditures to
cover costs up to 90 days before the beginning date of the initial budget
period of a new or competing renewal award if such costs: (1) are necessary to
conduct the project; and (2) would be allowable under the grant, if awarded,
without NIH prior approval. If specific expenditures would otherwise require
prior approval, the grantee must obtain NIH approval before incurring the cost.
NIH prior approval is required for any costs to be incurred more than 90 days
before the beginning date of the initial budget period of a new or competing
renewal award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project
(see theNIH
Grants Policy Statement).

6. Other Submission
Requirements and Information

Qualifications and
Experience

Applicants should
describe qualifications and experience in narrative
in the appropriate narrative sections of the application and in biosketches.
This description should specifically relate to the applicant’s ability to carry
out the goal of the FOA to study the impact of environment on the simultaneous development of the lung and immune system.

Multiple PI
Leadership Plan

The governance and
organizational structure of the leadership team (the PI with expertise in
pulmonary development and the PI with expertise in immunology) and the research
project should be described, including communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and scientific
responsibilities for the program should be delineated
for the PIs and other collaborators. If budget allocation is planned, the
distribution of resources to specific components of the project or the
individual PIs must be delineated (in the event of an award, the requested
allocation may be reflected in a footnote in the
NOGA). See the Multiple Principal Investigator website for more information http://grants.nih.gov/grants/multi_pi/index.htm.

FOA Meetings

Both PIs should
indicate their willingness to attend and fully
participate in a maximum of 5 meetings of the awardees in Bethesda, MD, during the program
cycle. These meetings will be used as a venue to discuss plans, results, and
potential collaboration among the program participants. Travel costs to attend at least one meeting per year in Bethesda, MD should be
included in the budget.

The
applicant organization must include its DUNS number in its Organization Profile
in the eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For
additional information, see “Frequently Asked Questions – Application Guide, Electronic
Submission of Grant Applications.”

PHS398
Research Plan Component Sections

Page
limitations of the PHS398 Research Plan component must be followed as outlined
in the SF424 (R&R) Application Guide. While each section of the Research
Plan component needs to be uploaded separately as a PDF attachment, applicants
are encouraged to construct the Research Plan component as a single document,
separating sections into distinct PDF attachments just before uploading the
files. This approach will enable applicants to better monitor formatting
requirements such as page limits. All attachments must be provided to NIH in
PDF format, filenames must be included with no spaces or special characters,
and a .pdf extension must be used.

All
application instructions outlined in the SF424 (R&R) Application Guide are
to be followed, incorporating "Just-in-Time" information concepts,
and with the following additional requirements:

Do not use the Appendix to circumvent the page limitations of
the Research Plan component. An application that does not comply with the
required page limitations may be delayed in the review process.

Resource Sharing
Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(a) Data Sharing Plan: Not Applicable

(b) Sharing Model Organisms: Regardless of
the amount requested, all applications where the development of model organisms
is anticipated are expectedto include a description of a
specific plan for sharing and distributing unique model organisms and related
resources, or state appropriate reasons why such sharing is restricted or not
possible. See Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested,
applicants seeking funding for a genome-wide association study are
expected to provide a plan for submission of GWAS data to the NIH-designatedGWAS data repository, or provide an appropriate explanation why
submission to the repository is not possible. A genome-wide association
study is defined as any study of genetic variation across the entire genome
that is designed to identify genetic associations with observable traits (e.g.,
blood pressure or weight) or the presence or absence of a disease or
condition. For further information see Policy for Sharing of Data
Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Foreign Applications
(Non-Domestic [non-U.S.] Entities)

Indicate how the proposed project has specific
relevance to the mission and objectives of the NIH/IC and has the potential for
significantly advancing the health sciences in the United States.

Section V. Application Review Information

1.
Criteria

Only
the review criteria described below will be considered in the review process.

2.
Review and Selection Process

Applications that are
complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review
group convened by the NHLBI and in
accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.

As part of the scientific peer review, all applications
will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned a priority
score.

Receive
a written critique.

Receive a second level of reviewby National Heart, Lung, and Blood Advisory
Council.

Applications submitted in response to this FOA will
compete for available funds with all other recommended applications submitted
in response to this FOA. The following will be considered in making funding
decisions:

Scientific
merit of the proposed project as determined by peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

Program balance
among proposed research protocols and balance of scientific expertise
among investigators.

The goals of NIH supported research are to advance our
understanding of biological systems, to improve the control of disease, and to
enhance health. In their written critiques, reviewers will be asked to comment
on each of the following criteria in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of these goals.
Each of these criteria will be addressed and considered in assigning the
overall score, and weighted as appropriate for each application. Note that an
application does not need to be strong in all categories to be judged likely to
have major scientific impact and thus deserve a meritorious priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.

Significance:Does this
study address an important problem? If the aims of the application are
achieved, how will scientific knowledge or clinical practice be advanced? What
will be the effect of these studies on the concepts, methods, technologies,
treatments, services, or preventative interventions that drive this field? Does the proposed study provide an
integrated view of pulmonary and immune system development within the context
of the model provided?

Approach:Are the
conceptual or clinical framework, design, methods, and analyses adequately
developed, well integrated, well reasoned, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? For applications designating multiple PDs/PIs, is the
leadership approach, including the designated roles and responsibilities,
governance, and organizational structure, consistent with and justified by the
aims of the project and the expertise of each of the PDs/PIs?Does the Leadership Plan for Multiple PIs describe a strong
organizational structure for the leadership team and
the research project to ensure that a comprehensive, integrated approach to the
research problem is in place, including communication plans, process for making
decisions on scientific direction, and procedures for resolving conflicts?

Innovation: Is
the project original and innovative? For example: Does the project challenge
existing paradigms; address an innovative hypothesis or critical barrier to
progress in the field? Does the project develop or employ novel concepts,
approaches, methodologies, tools, or technologies for this area?

Investigators:Are the
PD(s)/PI(s) and other key personnel appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to the experience level
of the principal investigator and other researchers? Do(es) the PD(s)/PI(s) and
investigative team bring complementary and integrated expertise to the project
(if applicable)?

Environment: Do(es) the scientific environment(s) in which the
work will be done contribute to the probability of success? Do the proposed
studies benefit from unique features of the scientific environment, or subject
populations, or employ useful collaborative arrangements? Is there evidence of
institutional support?

2.A.
Additional Review Criteria

In addition to
the above criteria, the following items will continue to be considered in the
determination of scientific merit and the rating:

Protection
of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. See the “Human Subjects Sections”
of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See the “Human Subjects Sections” of the PHS398
Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals
are to be used in the project, the adequacy of the plans for their care and use
will be assessed. See the “Other Research Plan Sections” of the PHS398 Research
Plan component of the SF424 (R&R).

Biohazards: If materials or procedures are proposed that are potentially
hazardous to research personnel and/or the environment, determine if the
proposed protection is adequate.

2.B. Additional Review Considerations

Budget and
Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. The priority score should not be
affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities
for furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions in other countries that are not
readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing
Plan(s)

When relevant, reviewers will be instructed to comment
on the reasonableness of the following Resource Sharing Plans, or the rationale
for not sharing the following types of resources. However, reviewers will not
factor the proposed resource sharing plan(s) into the determination of scientific
merit or priority score, unless noted otherwise in the FOA. Program staff
within the IC will be responsible for monitoring the resource sharing.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5. “Funding Restrictions.”

A final
progress report, invention statement, and Financial Status Report are required
when an award is relinquished when a recipient changes institutions or when an
award is terminated.

Section VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide
for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).Investigators should seek guidance from their
institutions, on issues related to institutional policies and local
institutional review board (IRB) rules, as well as local, state and federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them. All investigators proposing research involving
human subjects should read the "NIH Policy and Guidelines" on the
inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for Federal funding of research on hESCs can
be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators
funded by the NIH must submit or have submitted for them to the National
Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic
version of their final, peer-reviewed manuscripts upon acceptance for
publication, to be made publicly available no later than 12 months after the
official date of publication. The NIH Public Access Policy is
available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (HHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information," the "Privacy Rule," on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding
must be self-contained within specified page limitations. For publications
listed in the appendix and/or Progress report, Internet addresses (URLs) or
PubMed Central (PMC) submission identification numbers must be used for
publicly accessible online journal articles. Publicly accessible on-line
journal articles or PMC articles/manuscripts accepted for publication that are
directly relevant to the project may be included only as URLs or PMC
submission identification numbers accompanying the full reference in either
the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not
subject to the intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review. Awards are made under
the authorization of Sections 301 and 405 of the Public Health Service Act as
amended (42 USC 241 and 284) and under Federal Regulations
42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms
and conditions, cost principles, and other considerations described in the NIH Grants
Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a
40-hour week) for two years to the research. For further information, please
see: http://www.lrp.nih.gov/.